Life begins in utero typically. Prenatal environmental exposures, coupled with each zygote's genetics and epigenetic imprints, trace a life history path of health outcomes. The central theme of the Pittsburgh Specialized Center of Research on Sex and Gender Factors Affecting Women's Health is the "Genetic And Environmental Causes Of Adverse Pregnancy Outcomes." This major, but still under investigated, priority for women's health urgently requires multidisciplinary research both for the health of adult women and also for the health of developing fetuses and infants. For women, recurrent spontaneous abortions (RSA) are devastating. We have identified transgenerational transmission of a 'miscarriage gene' that may be an extreme example of deviant genomic imprinting. The implications for fetal outcomes are also of great importance, since in utero development of the fetus, both female and male, establishes the very foundation of the infant, adolescent, and adult. Three research projects along with two research cores and an administrative core are proposed under the directorship of Gerald Schatten, Ph.D. and Sarah Berga, M.D., Clinical Director. Project I, "Pregnancy Loss: Genomic Imprinting and Skewed X-Inactivation" (J. Richard Chaillet, MD, Ph.D., P.1), investigates DNA methylation defects in mice responsible for genomic imprinting as well as skewed X-chromosome inactivation, responsible for RSA in women, Project 11, "Epigenetic, Genetic and Environmental Regulation of Pregnancy in Primates" (Gerald Schatten, Ph.D., P.I. and Steve Caritis, MD, Co-P.I.), imaging primate pregnancies and inflammatory responses, addresses sex-specific genomic imprints in genetically controlled and experimentally-manipulated pregnancies. Project III (Julie DeLoia, Ph.D., P.I.), "Maternal and Fetal Consequences of Tobacco Smoke Exposure", analyzes the consequences of smoke exposure in pregnant women and in murine models to understand the interaction of 'genetic variants that jeopardize fetal development and pregnancy. The Imaging Core A performs noninvasive micro-PET and MRI imaging with specific probes, including transgenic MR11PET reporters. The Pregnancy Core B establishes and maintains pregnancies through conventional and artificial reproductive technologies (ART) in non-human primates and mice. The Administrative Core fosters intra- and inter-SCOR cooperation to facilitate and accelerate basic and clinical research. The multi-disciplinary, interactive, and collegial environments the new Pittsburgh Development Center at Magee-Women's Research Institute right on the contiguous campuses of the University of Pittsburgh and Carnegie-Mellon University, and brings together accomplished teams of clinical and basic investigators inspiring innovations in non-invasive imaging of pregnancy outcomes. Taken together, this comprehensive investigation will answer major women's health problems regarding the dynamic interplay among fetal and maternal genetics, sex-specific genomic imprints and consequences of our first environmental exposures. As such, it is an appropriate and complementary contributor to the ORWH's new SCOR program.